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John Davis: Why we work on Alzheimer’s disease

Q: Why is Alzheimer’s disease such an important medical problem?

John Davis: Alzheimer’s disease and the other dementias that are caused by other neurodegenerative diseases represent one of the biggest problems we face in our healthcare system today. At the moment, there are about 800,000 people living with dementias in the country and that number is only growing. By about 2050 we expect that to top 2 million people. That is twice the population of Birmingham, or over twice the population of Oxfordshire; it is a huge problem. Unfortunately, this also affects women particularly badly. A lot of the care that is required to look after people with dementia falls on the shoulders of women. And you may not realise this but dementia is one of the leading causes of death for women over 65.

Q: Why is a there a need to improve treatments for Alzheimer’s disease?

JD: The last medicine that was approved in the UK for treating patients with Alzheimer’s disease was approved in 2002. That is an awful long time ago, and doctors don't have many tools in their tool box with which to treat patients, so we desperately need new treatments. The other problem is that the treatments that we have today are all what we called symptomatic treatments. They treat the underlying memory loss, they try and improve your memory. Unfortunately, they do not work for a particularly long time and they do not tackle at all the progression of the disease. Although they may give you some benefit for a period of time, once their effect wears off then you are back on the course of a steady decline. We really do need to identify drugs that tackle the pathogenesis of the disease.

Q: How is the Oxford Drug Discovery Institute helping to discover new treatments for Alzheimer’s disease?

JD: The Oxford Drug Discovery Institute is one of three institutes that have been funded by the charity Alzheimer’s Research UK. Our role is to try and bring forward the basic research that is developed within academic settings such as the Universities, and start to turn that work into drugs. Alzheimer’s Research UK has a campaign called Defeat Dementia, and it aims to raise £100 million for research over 5 years. This a huge effort; it is all part of the Global Initiative, which the UK has played a leading role in, to tackle Alzheimer’s disease head on and meet the challenge of producing new treatments by 2025 - or at least the germ of a new treatment by 2025.

Q: What are the most important lines of research that have developed over the last 5-10 years?

JD: It has been a particularly interesting and exciting time over the last decade for research into Alzheimer’s and other neurodegenerative diseases. Over the next year or so we are going to see the pivotal trials for a number of anti-amyloid approaches, and that was the main thrust of many efforts over the last decade. Those results will be extremely exciting: they will tell us whether or not some of our basic hypothesis have been on the right track and we will be able to build on that.

Another very exciting area is the emergence of genetics. Because we can gather data now from large numbers of people we can look into the risk factors which might contribute towards a particular individual having Alzheimer’s disease. Those studies have honed in on one particular mechanism: neuroinflammation. There is a lot of excitement amongst academic groups and amongst pharma to dig deep into those neuroinflammatory mechanisms, and that is one area we will be focusing on in our Institute.

Q: Why does your line of research matter and why should we fund it?

JD: Alzheimer’s disease is a huge burden. It affects women a lot, it affects many many families; one in five families will have someone with dementia. We are all getting older, and there are less young people to look after us. It has been calculated that by 2017 or a few years after there won’t even be enough people there to care for people with Alzheimer’s disease. It is imperative that we find new drugs and find them fast. With the developing nations' populations living longer as well, globally there will be a huge number of people suffering from dementia. In the UK alone the costs of caring amount to about £24 billion; globally that is several hundred billion. That is equivalent to the GDP of small countries in the EU. It is a massive burden and we have to do something about it now.

Q: How does your research fit into translational medicine within the department?

JD: The Division of Medical Sciences has made translational research one of its main thrusts and our Department is all about translation. We are trying to develop these new areas of biology and bring them forward. The main job for us is to de-risk these new areas of biology, so that pharma, biotech and funders will pitch in to push the research onto the final delivery or a drug. That is our raison d'être, our whole purpose. In our Institute, we are chemists, biologists, many of us with pharma background. We know how to make drugs and we have been parachuted effectively into the academic system so that we can help achieve that translation.

John Davis

ARUK Oxford Drug Discovery Institute

Housed within the Target Discovery Institute, the Alzheimer’s Research UK Oxford Drug Discovery Institute (ODDI) juxtaposes drug discovery expertise alongside scientific and academic understanding of patients, disease mechanisms and model systems.
Led by Dr John Davis, ODDI aims to translate cutting edge academic science into drug discovery, and to prosecute projects from target to lead status, and beyond.

Why we work on Alzheimer’s disease

The burden caused by Alzheimer’s disease and other dementias represents one of the biggest problems for our healthcare systems. The last medicine was approved in 2002 and today we only have symptomatic treatments. ARUK-ODDI brings together chemists, biologist, psychiatrists and neuroscientists, many of them with pharmaceutical background, aiming to accelerate the discovery of novel and effective treatments.